The overall objective of this program is to define the events associated with stimulus-secretion coupling in mammalian gastric mucosa. Proposed objectives with reference to induction of acid secretion by secretagogues include definition of: a) the source of metabolic energy; b) target sites for cAMP and Ca ions and related regulatory processes; c) changes in membrane potential and transport of ions at both the apical and baso-lateral parietal cell membrane; d) measurement of the pH of the parietal cell secretory canaliculus; e) study the H ion K ion ATPase with respect to amino acid composition, catalytic and transport sites, vectorial and stoichiometric processes, location, and construction of a 3 dimensional model; and f) define the mechanisms of expansion of the secretory canaliculus following stimulus. The chief cell will be purified from this tissue and stimulus-secretion investigated with respect to pepsinogen. Hormone binding, cAMP and Ca ion levels as well as protein synthesis will be examined to establish a model to investigate stimulus-secretion coupling for zymogen granules.